miglustat / Generic mfg. - LARVOL DELTA

NEO1 modulates the A1 astrocyte polarization in subarachnoid hemorrhage through the cPLA2-MAVS signaling pathway. (PubMed, J Neuroinflammation) - "Furthermore, miglustat administration significantly attenuated neuroinflammation and improved neurological functional recovery following SAH. Collectively, our findings reveal that NEO1 inhibition alleviates A1 astrocyte polarization following SAH through the cPLA2-MAVS pathway."

Journal • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • GFAP

Cipaglucosidase alfa plus miglustat in Pompe disease: two non-ambulatory patients switching from high‑dose, high-frequency alglucosidase alfa. (PubMed, Neuromuscul Disord) - "We analyzed outcomes in two non-ambulatory patients in study ATB200-02 who received alg for >13 years (including >2 years' HDHF) before switching to cipa+mig (20 mg/kg + 260 mg every 2 weeks). The two patients experienced 11 non-serious adverse events (no infusion-associated reactions). Data provide information for clinicians considering a transition from HDHF alg to cipa+mig."

Journal • Fatigue • Lysosomal Storage Diseases • Metabolic Disorders • Pompe Disease • Rare Diseases

Miglustat in Alzheimer's Disease Associated With Heterozygous NPC1 Mutation: Exploratory Case Series and Preliminary Findings. (PubMed, Eur J Neurol) - "Based on our preliminary observations and hypothesis-generating findings, along with the growing evidence suggesting AD as a lipid disorder, miglustat should be further tested in a larger cohort of heterozygous NPC1 mutated patients and probably evaluated as a potential disease-modifying treatment for AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • NPC1

Miglustat as a Treatment for Adults with Tangier Disease Neuropathy: The MUSTANG N-of-1 Trial with 21 months Clinical Observation. (PubMed, Neurol Ther) - "Miglustat may be used to treat neurological complications of TD. This study showed that an n-of-1 study to inform a policy decision is practical and may offer hope to patients with rare diseases."

Journal • Frontotemporal Lobar Degeneration • Gaucher Disease • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Pain • Rare Diseases

EXPERIENCE OF MIGLUSTAT THERAPY IN PEDIATRIC PATIENTS WITH NIEMANN-PICK TYPE C DISEASE (SSIEM 2023) - No abstract available

Clinical • Genetic Disorders • Lysosomal Storage Diseases • Pediatrics

Investigating the Role of Miglustat in The Management of a Patient with Tangier’s Disease: An N-Of-1 Study with Alternating Periods of Intervention and Control (SSIEM 2023) - "These results support the therapeutic benefit of miglustat in TD and the importance of patient access to this treatment option."

Clinical • ABCA1

Generation of iPSC-derived human neuronal progenitors for the study of GM1 gangliosidosis. (SSIEM 2023) - "We tested the action of the substrate- specific inhibitor butyl-deoxynojirimycin (NB-DNJ), which alleviated the disease-related phenotypes of GM1-NPCs in vitro... iPSC-derived GM1-NPc recreated, in vitro, the biochemical and molecular phenotype of GM1 Gangliosidosis with absent β-gal activity and increased/malfunctioning of lysosomes. The accumulation of the ganglioside Gm1 at the neuronal level and its critical role in the pathogenesis of the disease were evaluated. The pathophysiological effects of GM1 cells were compared with the isogenic control line derived from the patient`s iPSCs and edited by the Crispr-Cas9 technique."

CNS Disorders • Genetic Disorders • Lysosomal Storage Diseases • GLB1

The SGLT2 Inhibitor Dapagliflozin Disrupts the Cell Cycle at High Concentrations Without Altering Glycosphingolipid (De Novo)Biosynthesis. (PubMed, Int J Mol Sci) - "Treatment options for glycosphingolipidoses, lysosomal storage diseases involving glycosphingolipids (GSLs), are currently limited to a few drugs that inhibit de novo GSL biosynthesis, such as eliglustat and miglustat (Zavesca®). While Genz-123346 significantly inhibited glycosphingolipid biosynthesis at concentrations as low as 1 µM, dapagliflozin, even up to 50 µM, had no effect on biosynthesis or de novo biosynthesis in either cell line. These results indicate that dapagliflozin, although assessing effects on the cell cycle, including proliferation at high concentrations, is not a suitable candidate for treating glycosphingolipid storage diseases by substrate reduction."

Journal • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

UDP-glucose ceramide glucosyltransferase promotes radioresistance via membrane reorganization to maintain redox balance in glioblastoma. (PubMed, Br J Cancer) - "These findings reveal a previously underexplored, membrane-centric mechanism of radioresistance in which UGCG orchestrates lipid raft remodeling to facilitate glutamine-dependent redox balance. This highlights UGCG as a potential therapeutic target to enhance the efficacy of radiotherapy in GBM."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • SLC1A5

Visual Recovery and Neurological Stabilization Following Miglustat Treatment in Pediatric CLN3 Disease. (PubMed, J Child Neurol) - "These preliminary findings suggest potential short-term clinical benefit of miglustat in pediatric patients with CLN3 disease, particularly when initiated early in the disease course. Further studies involving larger cohorts and longer follow-up are warranted to evaluate the safety and long-term efficacy of miglustat in this population."

Journal • CNS Disorders • Ophthalmology • Pediatrics

Effects of Miglustat Therapy on Infantile Type of Sandhoff and Taysachs Diseases (EMTISTD) (clinicaltrials.gov) - P3 | N=30 | Terminated | Sponsor: Tehran University of Medical Sciences | Trial completion date: Dec 2024 ➔ Sep 2025 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Sep 2025; The number of controls was insufficient compared to case.

Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Is Miglustat an Effective Treatment for CLN3 (Batten) Disease? (PubMed, Neurology) - No abstract available

Journal

Long-Term Open-Label Study Evaluating Oral Miglustat Treatment in Patients With Neuronal Ceroid Lipofuscinosis Type 3. (PubMed, Neurology) - "Miglustat showed a favorable safety profile and was associated with a slower rate of physical decline compared with historical controls. Limitations include small sample size, genetic heterogeneity, and open-label design."

Clinical • Journal • CNS Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Ketogenic Diet in Niemann-Pick Type C: Insights From a Case Report. (PubMed, Int J Dev Neurosci) - "In NPC patients treated with miglustat-particularly those experiencing seizures-a ketogenic diet may support neurological stabilization. A lower ratio KD may enhance long-term compliance."

Journal • CNS Disorders • Epilepsy • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Clinical characteristics and treatment outcomes in patients with Niemann-Pick disease type C (NP-C): a cross-sectional study. (PubMed, Orphanet J Rare Dis) - "This first comprehensive analysis of NP-C in Iran demonstrates the effectiveness of miglustat across multiple disease manifestations, particularly for visceral and cortical symptoms. While neurological symptoms generally stabilized, responses varied, emphasizing the need for individualized therapeutic approaches. Early diagnosis and intervention remain crucial for improving outcomes in this progressive neurodegenerative disorder."

Journal • Observational data • CNS Disorders • Cognitive Disorders • Developmental Disorders • Epilepsy • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Long-term efficacy and safety of arimoclomol in Niemann-Pick disease type C: Final results of the phase 2/3 NPC-002 48-month open-label extension trial. (PubMed, Mol Genet Metab) - P2/3 | "The OLE of the NPC-002 trial provides evidence for a sustained reduction in disease progression for at least 5 years in a heterogeneous population of NPC patients receiving arimoclomol in addition to routine clinical care, with no new safety concerns. These results align with the statistically significant and clinically meaningful reduction in disease progression observed over 12-months in the DB phase, further highlighting the potential of arimoclomol as an effective and well tolerated disease modifying treatment for NPC."

Journal • P2/3 data • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Serum neurofilament light protein as a biomarker in Niemann-Pick disease, type C1. (PubMed, Genet Med Open) - "Longitudinal analyses reveal a 26% reduction in serum NfL levels in individuals on miglustat, a therapeutic drug used off-label for the treatment of NPC1 in the United States of America...To help inform clinical trial design, our modeling predicts that a measurable reduction of serum NfL levels might be observed after 8 months of treatment with a potential drug exhibiting 10% to 20% efficacy. Our data suggest that NfL may be a useful serum biomarker for NPC1."

Biomarker • Journal • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment. (PubMed, J Inherit Metab Dis) - "Therapeutic development for NPC1 has been historically limited, with miglustat approved in some regions for off-label use and 2-hydroxypropyl-β-cyclodextrin currently under clinical investigation...Ongoing clinical trials and translational research are essential to accelerate biomarker qualification and regulatory approval of disease-modifying treatments. A comprehensive, mechanistically driven approach that integrates molecular, biochemical, and clinical endpoints is key to advancing precision medicine for NPC1."

Biomarker • Journal • Review • Ataxia • Cholestasis • CNS Disorders • Dystonia • Hepatology • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders • Rare Diseases • NEFL • NPC1

Naringenin and SMER28 target lysosomal reformation and rescue SPG11 and SPG15 Hereditary Spastic Paraplegia phenotypes. (PubMed, Pharmacol Res) - "Here we assessed the therapeutic potential of two FDA-approved compounds, tideglusib and naringenin, that target lysosomal function and regeneration, both registered for clinical use. Their effects were compared with those of SMER28 and of miglustat, the latter tested in a phase II clinical trial in SPG11 patients, in both SPG15 and SPG11 patient's derived cells and in the corresponding Drosophila models...Both compounds induced lysosomal tubulation, downstream of mTOR, promoting lysosomal reformation. Our work indicates that lysosomal reformation is a good strategy for HSPs with impaired lysosomal function and identifies naringenin as new modulator of this process, offering further hand to planning phase II clinical trials in SPG11-SPG15 patients."

Journal • Genetic Disorders

Efficacy and safety of efavirenz in Niemann-Pick disease type C. (PubMed, Neurotherapeutics) - P2 | "Efavirenz appears to be a safe, easy-to-use, new targeted therapeutic option which slows the rate of NPC progression. The benefits of efavirenz are greater if started earlier."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Dyslipidemia • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Efficacy results from a 12-month double-blind randomized trial of arimoclomol for treatment of Niemann-Pick disease type C (NPC): Presenting a rescored 4-domain NPC Clinical Severity Scale. (PubMed, Mol Genet Metab Rep) - P2/3 | "Arimoclomol has been approved in the US for treatment of Niemann-Pick disease type C (NPC) in combination with miglustat...The R4DNPCCSS is a valid and reliable measure of disease progression demonstrating consistent outcomes with the prespecified 5DNPCCSS endpoint. Arimoclomol significantly slowed disease progression through 12 months as measured by the R4DNPCCSS versus placebo."

Clinical • Journal • Ataxia • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Movement Disorders

BBDF101-01: An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of CLN3 Disease (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: Beyond Batten Disease Foundation | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders

Enzyme replacement therapies in adults with Pompe disease: from trials to real-world data. (PubMed, Curr Opin Neurol) - "The advent of two next-generation enzyme replacement therapies marks a new era in treating patients diagnosed with Pompe disease. Clinical trials and early real-world data suggest that they may be superior to alglucosidase alfa, the standard of care for the past 20 years, although head-to-head comparisons between all three treatments are lacking. More data will become available over the next 5 years, leading to better guidelines for starting, stopping and switching therapies based on a more personalized assessment of outcomes."

Journal • Real-world evidence • Pompe Disease

Neurogenin 2-induced central neurons from iPSC-established patients with NPC display attenuated neurite outgrowth while accumulating cholesterol. (PubMed, Biochim Biophys Acta Mol Cell Biol Lipids) - "Five iPSCs (3 NPC and 2 healthy individuals) carrying a doxycycline-inducible NGN2 (iPSCsTetON:NGN2) were generated, and edited cells efficiently differentiated into cortical neurons by 15 days...Miglustat, a drug approved for NPC in several countries, promoted neurite outgrowth and reduced unesterified cholesterol accumulation in LDL-treated NPC neurons...Collectively, our results indicate that neurons of NPC patients fail neurite extension due to suboptimal cholesterol transport to the membrane. This will be a valuable tool for NPC research to identify the pathological mechanisms of neuronal degeneration and to discover new therapeutics."

Journal • CNS Disorders • Dyslipidemia • Frontotemporal Lobar Degeneration • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • NEUROG2 • NPC1 • NPC2

Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL. (PubMed, Muscle Nerve) - P3 | "ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes."

Clinical • Journal • Retrospective data • Fatigue • Pompe Disease • Pulmonary Disease